Methionine metabolism in mammals has been studied by the following techniques: (1) analysis of the kinetic properties of four enzymes relevant to the pathway (s-adenosylmethionine synthetase, s- adenosylhomocysteine hydrolase, cystathionine synthase and betaine- homocysteine methyltransferase); (2) evaluation of the effect of diet and hormones on the levels of the relevant enzymes (cystathionase and 5- methyltetrahydrofolate-homocysteine methyltransferase as well as the four enzymes noted above); and (3) metabolism of methionine in the isolated, perfused rat liver. The pattern of methionine metabolism varies in the several rat tissues studied. Every tissue possesses the capacity to synthesize s- adenosylmethionine, to hydrolyze s-adenosylhomocysteine and to metabolize homocysteine. Homocysteine may be converted to either cystathionine or methionine. In some tissues both potentials are present. In other organs only one capacity exists. In liver methionine metabolism is regulated by the distribution of homocysteine between the cystathionine synthase and methyltetrahydrofolate transferase reactions. This distribution of homocycteine is governed by adaptive changes in the hepatic content of the enzymes.